Analysis of mercapturic acid conjugates of xenobiotic compounds using negative ionization and tandem mass spectrometry

Jones, A. Daniel; Winter, Carl K.; Buonarati, Michael H.; Segall, H. J.

doi:10.1002/bms.1200220109

Cited by 14 publications

(6 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fragmentation of [ + H]+ is simple, with a fragment at m/z 214 (arising from cleavage of the sulfuraliphatic carbon bond) accounting for most of the fragment ion intensity. Similar fragmentation has been observed for other thioether conjugates (21,22). These cumulative data strongly supported the atrazine mercapturate as accounting for the majority of the immunoreactive material initially seen in our ELISA.…”

Section: Resultssupporting

confidence: 88%

Determination of atrazine metabolites in human urine: Development of a biomarker of exposure

Lucas¹,

Jones²,

Goodrow³

et al. 1993

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

Enzyme-linked immunosorbent assays (ELISAs) are reported for the detection of atrazine and its principle metabolite in human urine. The ELISAs can be used with crude urine or following extraction and partial purification by methods described in this report. GC, MS, and HPLC techniques were used to confirm and complement the ELISA methods for qualitative and quantitative detection of urinary metabolites. A series of samples from workers applying this herbicide confirmed a mercapturic acid conjugate of atrazine as a major urinary metabolite. The mercapturate was found in concentrations at least 10 times that of any of the N-dealkylated products or the parent compound. Atrazine mercapturic acid was isolated from urine using affinity extraction based upon a polyclonal antibody for hydroxy-s-triazines and yielded products sufficiently pure for structure confirmation by MS/MS. In a pilot study monitoring applicators, a relationship between cumulative dermal and inhalation exposure and total amount of atrazine equivalents excreted over a 10-day period was observed. On the basis of these data, we propose that an ELISA for the mercapturate of atrazine could be developed as a useful marker of exposure.

show abstract

Section: Resultssupporting

confidence: 88%

Determination of atrazine metabolites in human urine: Development of a biomarker of exposure

Lucas¹,

Jones²,

Goodrow³

et al. 1993

Chem. Res. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally the method is highly sensitive with a detection limit of 0.1 ng of DHN-MA injected. This value is about 10-fold lower than that obtained for mercapturic conjugate analysis after derivatization and GC/electrocapture MS (21). Moreover, it can be expected that the general analysis scheme presented here should also be applicable to the determination of several other urinary mercapturic conjugates widely used as biomarkers of recent exposure to electrophilic chemicals (22).…”

Section: Discussionmentioning

confidence: 69%

1,4-Dihydroxynonene Mercapturic Acid, the Major End Metabolite of Exogenous 4-Hydroxy-2-nonenal, Is a Physiological Component of Rat and Human Urine

Alary¹,

Debrauwer²,

Fernandez³

et al. 1998

Chem. Res. Toxicol.

View full text Add to dashboard Cite

In the present study 1,4-dihydroxynonene mercapturic acid (DHN-MA), previously shown to be the major urinary metabolite of 4-hydroxy-2-nonenal (HNE) administered to the rat, was characterized and determined to be a normal constituent of rat and human urine. DHN-MA was excreted as a mixture of at least two stereoisomers as determined by ion trap LC-MS/MS/MS after solid-phase extraction and HPLC purification. The 24-h urinary excretion of this compound was about 10 ng and 5 microg for rat and human, respectively. This end metabolite of the lipid peroxidation product HNE could represent a specific and noninvasive biomarker.

show abstract

“…15 In the ESI mode, a similar fragmentation is also preferred by the protonated molecular ion [M C H] C of all three conjugates of VPA (m/z 304) studied giving rise to the product ion m/z 130. The enhanced sensitivity C ion of FVPA-GLN under CID gives rise to m/z 130 20 and the transition m/z 291 to 130 was therefore monitored for the IS and was appropriate for the assay.…”

Section: Resultsmentioning

confidence: 93%

Gas chromatography/negative ion chemical ionization mass spectrometry and liquid chromatography/electrospray ionization tandem mass spectrometry quantitative profiling ofN-acetylcysteine conjugates of valproic acid in urine: application in drug metabolism studies in humans

2000

View full text Add to dashboard Cite

We report a GC/NICI-MS assay and a LC/ESI-MS/MS assay for the analysis of N-acetylcysteine (NAC) conjugates of (E)-2,4-diene VPA (NAC I and NAC II) identified in humans. The assay also includes the analysis of the NAC conjugate of 4,5-epoxy VPA (NAC III), an identified metabolite in rats treated with 4-ene VPA for its use in metabolic studies in animals. The highly sensitive GC/MS assay was designed to monitor selectively the diagnostic and most abundant [M - 181](-) fragment anion of the di-PFB derivatives of NAC I, NAC II, and NAC IV, the internal standard (IS) and the PFB derivative of NAC III. The higher selectivity of LC/MS/MS methodology was the basis for an assay which could identify and quantitate the underivatized conjugates simultaneously using MRM of the diagnostic ions m/z 130 and 123 arising from the CID of their protonated molecular ions [MH](+). The GC/MS assay employed liquid-liquid extraction whereas the LC/MS/MS assay used a solid-phase extraction procedure. Linearity ranges of the calibration curves were 0.10-5.0microg ml(-1) by GC/MS and 0.10-1.0microg ml(-1) by LC/MS/MS for NAC I, NAC II and NAC III (r(2) = 0.999 or better). Both assays were validated for NAC I and NAC II and provided good inter- and intra-assay precision and accuracy for NAC I and NAC II. The LOQ by LC/MS/MS was 0.1microg ml(-1), representing 1 ng of NAC I and NAC II. The same LOQ (0.1microg ml(-1)) was observed by GC/MS and was equivalent to 100 pg of each metabolite. NAC III was detected at concentrations as low as 0.01 microg ml(-1) by both methods. The total urinary excretion of the NAC conjugates in four patients on VPA therapy was determined to be 0.004-0.088% of a VPA dose by GC/MS and 0.004-0. 109% of a VPA dose by LC/MS/MS.

show abstract

Analysis of mercapturic acid conjugates of xenobiotic compounds using negative ionization and tandem mass spectrometry

Cited by 14 publications

References 36 publications

Determination of atrazine metabolites in human urine: Development of a biomarker of exposure

Determination of atrazine metabolites in human urine: Development of a biomarker of exposure

1,4-Dihydroxynonene Mercapturic Acid, the Major End Metabolite of Exogenous 4-Hydroxy-2-nonenal, Is a Physiological Component of Rat and Human Urine

Gas chromatography/negative ion chemical ionization mass spectrometry and liquid chromatography/electrospray ionization tandem mass spectrometry quantitative profiling ofN-acetylcysteine conjugates of valproic acid in urine: application in drug metabolism studies in humans

Contact Info

Product

Resources

About